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Nuklearmedizin 2020; 59(05): 387-389
DOI: 10.1055/a-1164-5667
Case Report

[68Ga]Ga-DATA5m.SA.FAPi PET/CT: Specific Tracer-uptake in Focal Nodular Hyperplasia and potential Role in Liver Tumor Imaging

[68Ga]Ga-DATA5m.SA.FAPi PET/CT: Uptake in fokal nodulärer Hyperplasie und potentielle Anwendung zur Tumorbildgebung in der Leber
Barbara Kreppel
1   Department of Nuclear Medicine, University Medical Center Bonn, Bonn, Germany
,
Florian C. Gärtner
1   Department of Nuclear Medicine, University Medical Center Bonn, Bonn, Germany
,
Milka Marinova
2   Department of Radiology, University Medical Center Bonn, Bonn, Germany
,
Ulrike Attenberger
2   Department of Radiology, University Medical Center Bonn, Bonn, Germany
,
Michael Meisenheimer
1   Department of Nuclear Medicine, University Medical Center Bonn, Bonn, Germany
,
Marieta Toma
3   Department of Pathology, University Medical Center Bonn, Bonn, Germany
,
Glen Kristiansen
3   Department of Pathology, University Medical Center Bonn, Bonn, Germany
,
Georg Feldmann
4   Department of Internal Medicine III, University Medical Center Bonn, Bonn, Germany
,
Euy Sung Moon
5   Department of Nuclear Chemistry, Johannes Gutenberg University, Mainz, Germany
,
Frank Roesch
5   Department of Nuclear Chemistry, Johannes Gutenberg University, Mainz, Germany
,
Pieter Van Der Veken
6   Department of Pharmaceutical Sciences, Laboratory of Medical Biochemistry, University of Antwerp, Wilrijk, Belgium
,
Markus Essler
1   Department of Nuclear Medicine, University Medical Center Bonn, Bonn, Germany
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Background

Fibroblast activating protein (FAP) is a membrane bound serine protease up-regulated in activated fibroblasts. These are essential for tissue remodeling in wound healing, chronic inflammation as well as in carcinoma associated fibroblasts (CAF) in several types of cancer [1] [2] [5] [8] [9] [11]. Subject of recent developments are new 68Ga-labelled PET tracers that operate as FAP-specific enzyme inhibitors (FAPi). The inhibitor is a small molecule based on a 4.4-difluoroproline-quinoline motif with a carbonitrile warhead that binds to FAP and blocks its chemical reaction. This highly potent inhibitor, referred to as UAMC 1110, combines high affinity respectively high inhibition ability to FAP and in opposite towards DPPs and PREP [6]. Various tumors and proliferating tissue show an uptake of this tracer. FAPi shows rapid washout from normal tissue facilitating high-contrast images. This is particularly advantageous as the sensitivity of FDG-PET is low in regions with high or inhomogenous glucose metabolism such as brain, heart or the liver [4]. Therefore, FAPi-PET may be superior to FDG-PET in these regions. The new class of FAPi-radiopharmaceuticals utilizes a squaric acid (SA) motif as part of the structure connecting the inhibitor moiety UAMC 1110 with various chelators such as DOTA and DATA, yielding precursors of type DOTA.SA.FAPi or DATA5m.SA.FAPi. All compounds are of low nanomolar binding affinity to FAP and excellent selectivity towards other proteases [3].



Publication History

Article published online:
11 May 2020

© Georg Thieme Verlag KG
Stuttgart · New York

Letter to this article:

Re: [68Ga]Ga-DATA5m.SA.FAPi PET/CT: Specific Tracer-uptake in Focal Nodular Hyperplasia and potential Role in Liver Tumor ImagingNuklearmedizin 2020; 59(06): 455-455
DOI: 10.1055/a-1284-1920

 

  • References

  • 1 Acharya PS, Zukas A, Chandan V. et al. Fibroblast activation protein: a serine protease expressed at the remodeling interface in idiopathic pulmonary fibrosis. Hum Pathol 2006; 37: 352-360
    CrossrefPubMedGoogle Scholar
  • 2 Egger C, Cannet C, Gérard C. et al. Effects of the fibroblast activation protein inhibitor, PT100, in a murine model of pulmonary fibrosis. Eur J Pharmacol 2017; 809: 64-72
    CrossrefPubMedGoogle Scholar
  • 3 Moon ES. Targeting fibroblast activation protein (FAP): next generation PET radiotracers using squaramide coupled bifunctional DOTA and DATA5m chelators. submitted.
    Google Scholar
  • 4 Giesel FL, Kratochwil C, Lindner T. et al. 68Ga-FAPI PET/CT: Biodistribution and Preliminary Dosimetry Estimate of 2 DOTA-Containing FAP-Targeting Agents in Patients with Various Cancers. J Nucl Med 2019; 60: 386-392
    CrossrefPubMedGoogle Scholar
  • 5 Giuffrida P, Pinzani M, Corazza GR. et al. Biomarkers of intestinal fibrosis – one step towards clinical trials for stricturing inflammatory bowel disease. United European Gastroenterol J 2016; 4: 523-530
    CrossrefPubMedGoogle Scholar
  • 6 Jansen K, Heirbaut L, Verkerk R. et al. Extended structure-activity relationship and pharmacokinetic investigation of (4-quinolinoyl)glycyl-2-cyanopyrrolidine inhibitors of fibroblast activation protein (FAP). J Med Chem 2014; 57: 3053-3074
    CrossrefPubMedGoogle Scholar
  • 7 Koehne de Gonzalez AK, Salomao MA, Lagana SM. Current concepts in the immunohistochemical evaluation of liver tumors. World J Hepatol 2015; 7: 1403-1411
    CrossrefPubMedGoogle Scholar
  • 8 Levy MT, McCaughan GW, Abbott CA. et al. Fibroblast activation protein: a cell surface dipeptidyl peptidase and gelatinase expressed by stellate cells at the tissue remodelling interface in human cirrhosis. Hepatology 1999; 29: 1768-1778
    CrossrefPubMedGoogle Scholar
  • 9 López JI, Errarte P, Erramuzpe A. et al. Fibroblast activation protein predicts prognosis in clear cell renal cell carcinoma. Hum Pathol 2016; 54: 100-105
    CrossrefPubMedGoogle Scholar
  • 10 Rebouissou S, Bioulac-Sage P, Zucman-Rossi J. Molecular pathogenesis of focal nodular hyperplasia and hepatocellular adenoma. J Hepatol 2008; 48: 163-170
    CrossrefPubMedGoogle Scholar
  • 11 Rovedatti L, Di Sabatino A, Knowles CH. et al. Fibroblast activation protein expression in Crohn's disease strictures. Inflamm Bowel Dis 2011; 17: 1251-1253
    CrossrefPubMedGoogle Scholar